Hithereto, it has been known that a number of compounds which have relaxation activity on vascular smooth muscle by inhibiting influx of calcium ions into cells are useful in the treatment of diseases in cardiac circulatory. As such compounds, for example, calcium channel inhibitors and sodium channel inhibitors have been already developed, and, further, many studies on potassium channel activators have been made. Examples of such potassium channel activators include Pinacidil used frequently as a capillary vasodilator drug; Nicorandil used as an anti-stenocardia drug; and Cromakalim of Beecham Group plc used as an anti-hypertensive agent.
European Patent Publication No. 093,535 filed by Beecham Group, plc. in the title of "novel chromene and chroman" discloses benzopyran derivatives of formula(A) and salts thereof: ##STR4## wherein:
one of R.sup.a and R.sup.b is a hydrogen atom and the other is selected from the group consisting of a C.sub.1-6 alkyl- and alkoxycarbonyl, C.sub.1-6 alkyl-carbonyloxy, C.sub.1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C.sub.1-6 alkyl- and alkoxysulfinyl, C.sub.1-6 alkyl- and alkoxysulfonyl, C.sub.1-6 alkyl- and alkoxycarbonylamino, C.sub.1-6 alkyl- and alkoxysulfinylamino, C.sub.1-6 alkyl- and alkoxysulfonylamino, C.sub.1-6 alkyl- and alkoxythicarbonyl, C.sub.1-6 alkyl- and alkoxythiocarbonyloxy, C.sub.1-6 alkylthiomethyl, formyl, an optionally substituted aminosulfinyl, aminosulfonyl or aminocarbonyl, or a terminal substituted ethylenyl, --C(C.sub.1-6 alkyl) NOH, or --C(C.sub.1-6 alkyl)NNH.sub.2 group; or
one of R.sup.a and R.sup.b is nitro, cyano or a C.sub.1-6 alkylcarbonyl group and the other is methoxy or an optionally substituted amino group; PA1 one of R.sup.c and R.sup.d is a hydrogen atom or a C.sub.1-4 alkyl, and the other is a C.sub.1-4 alkyl group; or PA1 R.sup.c and R.sup.d together form a C.sub.2-5 polymethylene; PA1 X' is an oxygen or sulfur atom; PA1 Y' and Z' are hydrogen atoms or together form a single bond; and n is 1 or 2. PA1 R.sup.f is a hydrogen atom, lower alkyl or phenyl group; PA1 R.sup.g is a hydrogen atom or lower alkyl group; PA1 R.sup.h is a hydrogen atom or a hydroxy group; and, R.sup.i is a hydrogen atom; or R.sup.h and R.sup.i together form a C--C bond; and PA1 R.sup.j is an aryl- or N-heteroaryl group whose 2-position is a hydroxy group, or, an N-oxide group in case of N-heteroaryl group. PA1 R.sup.1 is F, Cl, Br, I, OH, OA, OAc, SA, NO.sub.2, NH.sub.2, NHA, NA.sub.2, CH or COOA; PA1 R.sup.m is H, OH, OA or OAc and R.sup.n is H; or R.sup.m and R.sup.n together form a single bond; PA1 R.sup.O is an optionally mono- or di-substituted pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxohydropyridyl, oxodihydropyridyl, oxodihydropyridazinyl, oxodihydropyrimidinyl, oxodihydropyrazinyl, 2-pyrrolidinon-1-yl or 3-oxocyclopenten-1-yl with A, F, Cl, Br, I, OH, OA, OAc, SH, NO.sub.2, NH.sub.2, NHAc, COOH and/or COOA; PA1 R.sup.p and R.sup.q are each independently H, A, HO, AO, CHO, ACO, ACS, HOOC, AOOC, AO--CS, ACOO, A--CS--O, hydroxyalkyl, mercaptoalkyl, NO.sub.2, NH.sub.2, NHA, NA.sub.2, CN, F, Cl, Br, I, CF.sub.3, ASO, ASO.sub.2, AO--SO, AO--SO.sub.2, ACNH, AO--CO--NH, N.sub.2 HSO, HANSO, A.sub.2 NSO, H.sub.2 NSO.sub.2, HANSO.sub.2, A.sub.2 NSO.sub.2, H.sub.2 NCO, HANCO, A.sub.2 NCO, A.sub.2 NCS, HANCS, A.sub.2 NCS, ASONH, ASO.sub.2 NH, ASO--ONH, AOSO.sub.2 NH, ACO-alkyl, nitroalkyl, cyanoalkyl, A--C(.dbd.NOH) or A--C.dbd.(NNH.sub.2); PA1 R.sup.r is H or A; PA1 Z is O, S, NH or a single bond; PA1 A represents a C.sub.1-6 alkyl group; PA1 -alkyl represents a C.sub.1-6 alkylene; and PA1 Ac represents a C.sub.1-8 alkanoyl or C.sub.7-11 aroyl group. PA1 R.sub.2 is a C.sub.1-4 straight or branched alkyl group; PA1 R.sub.3 is a C.sub.1-4 straight or branched alkyl group, ##STR9## wherein R.sup.G and R.sup.H are, each independently, a C.sub.1-6 alkyl group or an optionally substituted phenyl group with a halogen atom, or a straight or branched C.sub.1-3 alkyl group; A and B are, each independently, S or O; and Z is a C.sub.1-3 straight or branched alkyl group; PA1 X is N or N.fwdarw.O, provided, however, when X is in 2-position, ##STR10## Y is a hydrogen or halogen atom, or an amino, hydroxy, lower alkoxy or lower alkyl group. PA1 R.sub.1 is --CN or --NO.sub.2 ; PA1 R.sub.2 is a methyl group; PA1 R.sub.3 is a methyl group, ##STR11## X is N.fwdarw.O, provided, however, when X is in 2-position, R.sub.3 is not a methyl group; and PA1 Y is H. PA1 R.sub.1 is --CN or --NO.sub.2 ; PA1 R.sub.2 is a methyl group; PA1 R.sub.3 is a methyl group, ##STR12## X is N.fwdarw.O, provided, however, when X is in 2-position, R.sub.3 is not a methyl group; and PA1 Y is H.
Further, European Patent Publication No. 298,452 A2 filed by F. Hoffmann La Roche & Co. discloses benzopyran derivatives of formula(B) and pharmaceutical compositions containing same: ##STR5## wherein: R.sup.e is a hydrogen or halogen atom, or a trifluoromethyl, nitro, cyano, a lower alkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkanoyl, carbamoyl or mono- or di(lower alkyl) carbamoyl group;
Korean Patent Application No. 91-4602 filed by Merck Patent Gesellshaft mit beschrankter Haftung discloses a chromane derivative of formula(C) and a salt thereof: ##STR6## wherein R.sup.k is H or A;
The above compounds have been reported to be useful in the treatment of hypertension. However, another use of the compounds was reported in such references as Br. J. Pharmacol. 89, 395-405(1986), Br. J. Pharmacol. 165, 231-239(1989), and Br. J. Pharmacol. 95, 765-770(1988): i.e., the compounds may be used as a bronchodilator in addition to a blood pressure-lowering agent, since they relax smooth muscle by enhancing the hyperpolarization of the plasma membrane of a cell.
It has now been found that a novel class of benzopyrans have superior effectiveness in the treatment of both hypertension and asthma.